基质金属蛋白酶 7 在肺纤维化突变小鼠模型中的表达和顶端上皮缺陷。

Matrix Metalloproteinase 7 Expression and Apical Epithelial Defects in Mutant Mouse Model of Pulmonary Fibrosis.

机构信息

Laboratory of Dr. Narasaiah Kolliputi, Department of Internal Medicine, Division of Allergy/Immunology, College of Medicine, University of South Florida Morsani, Tampa, FL 33612, USA.

Departments of Medicine and Pediatrics, Division of Allergy/Immunology, College of Medicine, University of South Florida, Tampa, FL 33612, USA.

出版信息

Biomolecules. 2022 Feb 9;12(2):283. doi: 10.3390/biom12020283.

DOI:10.3390/biom12020283

PMID:35204783

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8961514/

Abstract

Abnormalities in airway epithelia and lung parenchyma are found in mutant mice, which develop pulmonary fibrosis after hyperoxic insult. Microarray and ingenuity pathway analysis (IPA) show numerous transcripts involved in ciliogenesis are downregulated in 14-month (14 M) -old mouse lung compared with wild-type C57BL/6. Lung epithelium of mice demonstrate apical abnormalities of ciliated and club cells in the bronchial epithelium on transmission electron microscopy (TEM). Matrix metalloproteinase 7 (MMP7) regulates of ciliogenesis and is a biomarker for idiopathic pulmonary fibrosis (IPF) in humans. transcript and protein expression are significantly upregulated in 14 M mutant mouse lung. MMP7 expression is also increased in bronchoalveolar lavage fluid (BAL). Immunohistochemistry is localized MMP7 to bronchial epithelial cells in the mutant. In conclusion, MMP7 is upregulated in the aged mouse model, which displays abnormal ciliated cell and club cell morphology. This mouse model can facilitate the exploration of the role of MMP7 in epithelial integrity and ciliogenesis in IPF. The mutant mouse is proposed as a model for IPF.

摘要

气道上皮和肺实质的异常在突变小鼠中被发现，这些小鼠在高氧损伤后会发展为肺纤维化。微阵列和 ingenuity 通路分析（IPA）显示，与野生型 C57BL/6 相比，14 个月（14M）龄的突变鼠肺中有许多参与纤毛发生的转录本下调。透射电镜（TEM）显示，突变鼠的支气管上皮中，纤毛细胞和 club 细胞的顶端出现异常。基质金属蛋白酶 7（MMP7）调节纤毛发生，是人类特发性肺纤维化（IPF）的生物标志物。在 14M 龄的突变鼠肺中，MMP7 的转录本和蛋白表达显著上调。MMP7 在支气管肺泡灌洗液（BAL）中的表达也增加。免疫组织化学将 MMP7 定位在突变的支气管上皮细胞中。总之，MMP7 在显示异常纤毛细胞和 club 细胞形态的老年突变鼠模型中上调。该小鼠模型可促进 MMP7 在 IPF 中上皮完整性和纤毛发生中的作用的探索。该突变鼠被提议作为 IPF 的模型。